•Fig. 18.22 Pressure-flowrelationshipinthevascularbedoftheskeletalmuscle.Filled (red) circles representtheflowratesobtainedimmediatelyafterabruptchangesinperfusionpressurefromthecontrollevel(thepointwherelinescross).Open (blue) circles representthesteady-stateflowratesobtainedatthenewperfusionpressure.(RedrawnfromJonesRD,BerneRM.Circ Res. 1964;14:126.)0 20 40 60 10080 120 140 160 180 0 2 4 6 8 10 12 Perfusion pressure (mm Hg) Muscle blood flow (mL/min/100 g)
Over the pressure range of 20 to 120 mm Hg, the steady-state flow is relatively constant. Calculation of hydraulic resistance (pressure/flow) across the vascular bed during steady-state conditions shows that the resistance vessels constrict with an elevation in perfusion pressure but dilate with a reduction in perfusion pressure. This response to perfusion pressure is independent of the endothelium because it is identical in intact vessels and in vessels that have been stripped of their endothelium. According to the myogenic mechanism, vascular smooth muscle contracts in response to an increase in the pressure difference across the wall of a blood vessel (transmural pressure), and it relaxes in response to a decrease in transmural pressure. The signaling mechanisms that allow distention of a vessel to elicit contraction are unknown. However, because stretch of vascular smooth muscle has been shown to raise intracellular [Ca++], an increase in transmural pressure is believed to activate membrane calcium channels.
Transientreceptorpotential(TRP)channelshavebeenimplicatedinthemyogenicmechanism.ThesechannelsaremammalianhomologuesofaDrosophila melanogaster genethat,whenmutated,allowsonlyatransientresponsetoasustainedlightstimulus.Thepressure-inducedvasoconstrictiveresponseofanartery(myogenicresponse)appearstohavethefollowingsignalpath:pressure → increasedphospholipaseCactivity→ synthesisofdiacylglycerol→ activationofTRPchannel→ smoothmuscledepolarizationandopeningofL-typecalciumchannelsthatincreaseintracellular[Ca++]andmuscletone.Thisisameansofregulatingvascularresistance.OtherTRPchanneltypeshavebeenproposedtoparticipateinchronichypoxicpulmonaryhypertensionandinthevasoconstrictioncausedbytheα-adrenergicagonistnorepinephrine.
In normal subjects, blood pressure is maintained at a fairly constant level via the baroreceptor reflex. Hence, the myogenic mechanism may play little role in regulating blood flow to tissues under normal conditions. However, when a person changes from a lying to a standing position, transmural pressure rises in the lower extremities, and the precapillary vessels constrict in response to this imposed stretch.
, the endothelium lining the vasculature produces a number of substances that can relax (e.g., nitric oxide) or contract (e.g., angiotensin II and endothelin) vascular smooth muscle. Thus the endothelium plays an important role in regulating blood flow to specific vascular beds.
The metabolic activity of a tissue governs blood flow in that tissue. Any intervention that results in inadequate O2 supply prompts the formation of vasodilator metabolites that are released from the tissue and act locally to dilate the resistance vessels. When the metabolic rate of the tissue increases, or when O2 delivery to the tissue decreases, more vasodilator substances are released (see
Chapter 17).